Drug lipophilicity represents a major concern in the development of efficient oral drug delivery and affects a substantial number of new drug candidates. Whereas several technologies are now available to improve the dissolution of lipophilic drugs (e.g. use of surfactants, prodrugs, cyclodextrin inclusions, lipid based formulations, microemulsions, liposomes) these methods are usually complex to perform. Therefore, there is still a need for improved and economical dosage forms having appropriate biopharmaceutical properties.
Nanotechnologies have become an important aspect in the development of improved drug delivery systems. Besides the nanosizing of the active ingredient itself, formulators have also considered the use of nanosized excipients.
Mesoporous materials have pores within their structures which can be loaded with active ingredients. Mesoporous materials are particularly suitable drug delivery carriers for poorly soluble drugs. Once the drug is loaded inside the pores of the mesoporous material, it is believed that the drug maintains in an amorphous or molecularly dispersed state due to a lack of space to crystallize. The drug can be loaded inside of the mesoporous carrier and/or mesoporous matrix and released for dissolution in an aqueous environment.
Porous silica materials have already been disclosed in the prior art. Mesoporous silicas, such as the MCM family, were materials prepared first by the Mobil Oil Company. Several other methods have been developed leading to a great variety of materials having e.g. different pore shapes and size distributions. Examples of such materials are the SBA-15 or 157 MSU products. These materials are for example disclosed in the review of Carrillo et al. “Well ordered mesoporous interconnected silica spheres prepared using extremely low surfactant concentrations”, Mater. Chem. Phys. 129 (2011) 261-269. However, these materials are difficult to formulate since they exhibit poor flowability and compression properties.
The article of Vialpando et al., J. of Pharm. Sc. (2013) discloses a comparison between the agglomerations of ordered and non-ordered mesoporous silica materials made by steam and melt granulations. According to Vialpando, the active ingredient on the surface of the particles remains in a crystallized form and does not therefore allow achieving an improved dissolution.
However, the properties of the cited prior art materials are not fully satisfying for poorly soluble drugs. Particularly, it appears that the loading capability of these carriers remains limited and that the dissolution of the active ingredient can further be increased.